期刊
NATURE IMMUNOLOGY
卷 21, 期 11, 页码 1346-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41590-020-0769-3
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资金
- JSPS [17K18388, 18J21161]
- Ministry of Education, Culture, Sports, Science and Technology of Japan [18J21551]
- Project for Cancer Research and Therapeutic Evolution (P-CREATE) [16cm0106301h0001, 18cm0106502s0403, 18cm0106340h0001]
- Development of Technology for Patient Stratification Biomarker Discovery grant [19ae0101074s0401]
- Leading Advanced Projects for Medical Innovation (LEAP) from the Japan Agency for Medical Research and Development (AMED) [18am0001001h9905]
- National Cancer Center Research and Development Fund [28-A-7, 31-A-7]
- Naito Foundation
- Takeda Science Foundation
- Kobayashi Foundation for Cancer Research
- Novartis
- Bristol-Myers Squibb
- SGH Foundation
- Ono Pharmaceutical Co. Ltd.
- [17H06162]
- [16K15551]
- [17J09900]
- Grants-in-Aid for Scientific Research [18J21551, 18J21161, 17K18388] Funding Source: KAKEN
Checkpoint blockade is effective in only a subset of patients; therefore, biomarkers that can predict efficacy would be clinically highly valuable. Nishkawa and colleagues develop a biomarker based on PD-1 positivity of effector and regulatory T cells in the tumor microenvironment that accurately predicts the effectiveness of checkpoint blockade in patients. Immune checkpoint blockade has provided a paradigm shift in cancer therapy, but the success of this approach is very variable; therefore, biomarkers predictive of clinical efficacy are urgently required. Here, we show that the frequency of PD-1(+)CD8(+)T cells relative to that of PD-1(+)regulatory T (T-reg) cells in the tumor microenvironment can predict the clinical efficacy of programmed cell death protein 1 (PD-1) blockade therapies and is superior to other predictors, including PD ligand 1 (PD-L1) expression or tumor mutational burden. PD-1 expression by CD8(+)T cells and T(reg)cells negatively impacts effector and immunosuppressive functions, respectively. PD-1 blockade induces both recovery of dysfunctional PD-1(+)CD8(+)T cells and enhanced PD-1(+)T(reg)cell-mediated immunosuppression. A profound reactivation of effector PD-1(+)CD8(+)T cells rather than PD-1(+)T(reg)cells by PD-1 blockade is necessary for tumor regression. These findings provide a promising predictive biomarker for PD-1 blockade therapies.
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